Juvenile Limb-Girdle Myasthenia Gravis

Rodolico, Carmelo; Pastura, C.; Sinicropi, S.; Girlanda, Paolo; Toscano, Antonio; Messina, C; Vita, Giuseppe

doi:10.1055/s-2005-872879

Cited by 3 publications

(3 citation statements)

References 12 publications

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“…DOK7 CMS can be distinguished from a second separate subset of CMS with proximal muscle weakness in which DOK7 mutations were not identified. Muscle biopsies in these patients show subsarcolemmal inclusions visible on electron microscopy, which are not seen in the DOK7 patients 18–21 . They are notable for a more exclusively “limb girdle” pattern of muscle weakness, and a greater sparing of the ocular, bulbar, respiratory, and distal muscles.…”

Section: The Dok‐7 Neuromuscular Junction Synaptopathymentioning

confidence: 78%

“…biopsies in these patients show subsarcolemmal inclusions visible on electron microscopy, which are not seen in the DOK7 patients. [18][19][20][21] They are notable for a more exclusively "limb girdle" pattern of muscle weakness, and a greater sparing of the ocular, bulbar, respiratory, and distal muscles. Onset was again associated with mobility problems that, in our experience, occurred later than for DOK7 CMS.…”

Section: The Dok-7 Neuromuscular Junction Synaptopathymentioning

confidence: 99%

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Congenital Myasthenic Syndromes and the Formation of the Neuromuscular Junction

Beeson

Webster

Cossins

et al. 2008

Annals of the New York Academy of Sciences

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The congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders affecting neuromuscular transmission. Underlying mutations have been identified in at least 11 different genes. The majority of CMS patients have disorders due to mutations in postsynaptic proteins. Initial studies focused on dysfunction of the acetylcholine receptor (AChR) itself as the major cause of CMS. However, it is becoming apparent that mutations of proteins involved in clustering the AChR and maintaining neuromuscular junction structure form important subgroups. Analysis of the mutations in the AChR-clustering protein, rapsyn, show diverse causes for defective AChR localization and suggest that the common mutation rapsyn-N88K results in AChR clusters that are less stable than those generated by wild-type rapsyn. More recently, mutations in the newly identified endplate protein Dok-7 have been shown to affect AChR clustering and the generation and maintenance of specialized structures at the endplate. Dok-7 binds MuSK and many of the mutations of DOK7 impair the MuSK signaling pathway. Components of this pathway will provide attractive gene candidates for additional forms of CMS. The phenotypic characteristics of the different CMS in which muscle groups may be differentially affected not only provide clues for targeted genetic screening, but also pose further intriguing questions about underlying molecular mechanisms.

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Section: The Dok‐7 Neuromuscular Junction Synaptopathymentioning

confidence: 78%

Section: The Dok-7 Neuromuscular Junction Synaptopathymentioning

confidence: 99%

Congenital Myasthenic Syndromes and the Formation of the Neuromuscular Junction

Beeson

Webster

Cossins

et al. 2008

Annals of the New York Academy of Sciences

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“…Limb-girdle MG was reported in 3.8% of adults. 19 Limb-girdle phenotype is often seen in CMS 9,20 and in hereditary or acquired myopathies. 19,20 However, most of our patients with isolated limb-girdle weakness were seropositive, confirming a diagnosis of autoimmune MG.…”

Section: Discussionmentioning

confidence: 99%

Treatment outcome in juvenile‐onset myasthenia gravis

et al. 2019

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Introduction Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction. Approximately 10%–15% of MG patients have juvenile (<18 years of age) onset. We aimed to assess the clinical course, outcome, and subjectively perceived health status of a cohort of juvenile MG patients. Methods This was a retrospective analysis of medical records of 101 patients followed by a cross‐sectional questionnaire study. Results The mean age of patients was 12.8 years at onset and 13.7 years at diagnosis. Ninety percent of the patients were seropositive. Over 40% of the patients were treated with immunosuppression and over 80% underwent thymectomy. The mean Myathenia Gravis Activities of Daily Living (MG‐ADL) scale score was 2.48. At last follow‐up, 30.9% of patients were in complete, stable remission; 77.8% perceived their health as good. Discussion The treatment outcome for juvenile MG is favorable, with a marked reduction of symptoms and good day‐to‐day activity achieved for most patients. Muscle Nerve 59:549–549, 2019

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Clinical features of the DOK7 neuromuscular junction synaptopathy

Palace

Lashley

Newsom‐Davis

et al. 2007

Brain

111

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Mutations in DOK7 have recently been shown to underlie a recessive congenital myasthenic syndrome (CMS) associated with small simplified neuromuscular junctions ('synaptopathy') but normal acetylcholine receptor and acetylcholinesterase function. We identified DOK7 mutations in 27 patients from 24 kinships. Mutation 1124_1127dupTGCC was common, present in 20 out of 24 kinships. All patients were found to have at least one allele with a frameshift mutation in DOK7 exon 7, suggesting that loss of function(s) associated with the C-terminal region of Dok-7 underlies this disorder. In 15 patients, we were able to study the clinical features in detail. Clinical onset was usually characterized by difficulty in walking developing after normal motor milestones. Proximal muscles were usually more affected than distal, leading to a 'limb-girdle' pattern of weakness; although ptosis was often present from an early age, eye movements were rarely involved. Patients did not show long-term benefit from anticholinesterase medication and sometimes worsened, and where tried responded to ephedrine. The phenotype can be distinguished from 'limb-girdle' myasthenia associated with tubular aggregates, where DOK7 mutations were not detected and patients respond to anticholinesterase treatments. CMS due to DOK7 mutations are common within our UK cohort and is likely to be under-diagnosed; recognition of the phenotype will help clinical diagnosis, targeted genetic screening and appropriate management.

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Juvenile Limb-Girdle Myasthenia Gravis

Cited by 3 publications

References 12 publications

Congenital Myasthenic Syndromes and the Formation of the Neuromuscular Junction

Congenital Myasthenic Syndromes and the Formation of the Neuromuscular Junction

Treatment outcome in juvenile‐onset myasthenia gravis

Clinical features of the DOK7 neuromuscular junction synaptopathy

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